Oxygen chemoreceptor inhibition by dopamine D<sub>2</sub> receptors in isolated zebrafish gills
Bibliographic record
Abstract
Abstract Dopamine is an essential modulator of oxygen sensing and control of ventilation and is the most well described and abundant neurotransmitter in the mammalian carotid body. Little is known of the evolutionary significance of dopamine in oxygen sensing, or whether it plays a similar role in anamniotes. In the model vertebrate, zebrafish (Danio rerio), presynaptic dopamine D2 receptor (D2R) expression was demonstrated in gill neuroepithelial cells (NECs), analogues of mammalian oxygen chemoreceptors; however, a mechanism for dopamine and D2R in the gills had not been defined. The present study tested the hypothesis that presynaptic D2Rs provide a feedback mechanism attenuating the chemoreceptor response to hypoxia. Using an isolated gill preparation from Tg(elavl3:GCaMP6s) zebrafish, we measured hypoxia‐induced changes in intracellular Ca2+ concentration ([Ca2+]i) in NECs and postsynaptic neurons. Activation of D2R with dopamine or specific D2R agonist, quinpirole, decreased hypoxic responses in NECs; whereas D2R antagonist, domperidone, had the opposite effect. Addition of SQ22536, an adenylyl cyclase (AC) inhibitor, decreased the effect of hypoxia on [Ca2+]i, similar to dopamine. Activation of AC by forskolin partially recovered the suppressive effect of dopamine on the Ca2+ response to hypoxia. Furthermore, we demonstrate that the response to hypoxia in postsynaptic neurons was dependent upon innervation with NECs, and was subject to modulation by activation of presynaptic D2R. Our results provide the first evidence of neurotransmission of the hypoxic signal at the NEC‐nerve synapse in the gill and suggest that a presynaptic, modulatory role for dopamine in oxygen sensing arose early in vertebrate evolution. image Key points For the first time, we present an experimental model that permits imaging of intracellular Ca2+ in identified oxygen chemoreceptors in zebrafish using GCaMP in a whole/intact sensing organ. The hypoxic response of zebrafish chemoreceptors is attenuated by dopamine through a mechanism involving D2 receptors and adenylyl cyclase. Zebrafish oxygen chemoreceptors send a hypoxic signal to postsynaptic (sensory) neurons. Postsynaptic neuronal responses to hypoxia are modulated by presynaptic D2 receptors, suggesting a link between chemoreceptor inhibition by dopamine and modulation of the hypoxic ventilatory response. Our results suggests that a modulatory role for dopamine in oxygen sensing arose early in vertebrate evolution.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".